Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with more than 200 entities and relevant differences in disease course and prognosis. Little data is available on hospitalisation patterns in ILD. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for hospitalisations. Reasons for hospitalisation were classified as all cause, ILD-related and respiratory hospitalisations, and patients were analysed for frequency of hospitalisations, time to first non-elective hospitalisation, mortality and progression-free survival. Additionally, the risk for hospitalisation according to GAP index and ILD subtype was calculated by Cox proportional-hazard models as well as influencing factors on prediction of hospitalisation by logistic regression with forward selection. RESULTS: In total, 601 patients were included. 1210 hospitalisations were recorded during the 6 months prior to registry inclusion until the last study visit. 800 (66.1%) were ILD-related, 59.3% of admissions were registered in the first year after inclusion. Mortality was associated with all cause, ILD-related and respiratory-related hospitalisation. Risk factors for hospitalisation were advanced disease (GAP Index stages II and III) and CTD (connective tissue disease)-ILDs. All cause hospitalisations were associated with pulmonary hypertension (OR 2.53, p = 0.005). ILD-related hospitalisations were associated with unclassifiable ILD and concomitant emphysema (OR = 2.133, p = 0.001) as well as with other granulomatous ILDs and a positive smoking status (OR = 3.082, p = 0.005). CONCLUSION: Our results represent a crucial contribution in understanding predisposing factors for hospitalisation in ILD and its major impact on mortality. Further studies to characterize the most vulnerable patient group as well as approaches to prevent hospitalisations are warranted.

Disease trajectories in interstitial lung diseases - data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5-10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression. RESULTS: Within the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001). CONCLUSION: Disease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful.

Krebs von den Lungen-6 as a Potential Predictive Biomarker in Fibrosing Interstitial Lung Diseases.

BACKGROUND: As fibrosing interstitial lung diseases (fILDs) are associated with high mortality, monitoring of disease activity under treatment is highly relevant. Krebs von den Lungen-6 (KL-6) is associated with the presence and severity of different fILDs, mainly in Asian patient populations. OBJECTIVES: Our aim was to evaluate KL-6 as a predictive biomarker in fILDs in Caucasian patients. METHODS: Consecutive patients with fILDs were recruited prospectively and serum concentrations of KL-6 were measured at baseline (BL), after 6 and 12 months (6 Months, 12 Months). Clinical characteristics including pulmonary function tests were assessed at 6-monthly visits and correlated with KL-6 BL levels as well as with KL-6 level changes. RESULTS: A total of 47 fILD patients were included (mean age: 65 years, 68% male). KL-6 levels at BL were significantly higher in fILD patients than in healthy controls (n = 44, mean age: 45, 23% male) (ILD: 1,757 ± 1960 U/mL vs. control: 265 ± 107 U/mL, p < 0.0001). However, no differences were noted between ILD subgroups. KL-6 decreased significantly under therapy (6M∆BL-KL6: -486 ± 1,505 mean U/mL, p = 0.032; 12M∆BL-KL6: -547 ± 1,782 mean U/mL, p = 0.041) and KL-6 level changes were negatively correlated with changes in pulmonary function parameters (forced vital capacity [FVC]: r = -0.562, p < 0.0001; DLCOSB: r = -0.405, p = 0.013). While neither absolute KL-6 levels at BL nor KL-6 level changes were associated with ILD progression (FVC decline ≥10%, DLCOSB decline ≥15% or death), patients with a stable FVC showed significantly decreasing KL-6 levels (p = 0.022). CONCLUSIONS: A decline of KL-6 under therapy correlated with a clinically relevant stabilization of lung function. Thus, KL-6 might serve as a predictive biomarker, which however must be determined by larger prospective cohorts.

How Informed Are German Patients with Pulmonary Sarcoidosis about Their Disease?

BACKGROUND: Sarcoidosis is a multisystemic disease with a heterogenous course of disease. Comprehensive information about the complexity and treatment indications is essential for improving patient knowledge and adhering to therapy. OBJECTIVES: The aim of our study was to investigate the level and resources of information in patients with sarcoidosis and to analyze differences in patient subgroups including age and gender. METHODS: We conducted a questionnaire-based online survey in Germany and three semi-structured focus group interviews. The interviews were evaluated independently by two investigators using a structured qualitative content analysis. RESULTS: A total of 402 completed questionnaires were analyzed, 65.8% of participants were women, and the mean age was 53 years. The majority of patients felt well informed about their disease in general (59.4%), but 40.6% were inadequately informed. The most relevant information gaps related to the future perspective (70.6%) as well as fatigue and diffuse pain (63.9%). Most patients received information from their treating pulmonologist (72.1%). 94% used the internet, especially homepages of patient support groups (75.2%). Male participants more often reported being well informed about their disease and were more satisfied with the information (p = 0.001). During the interviews, patients expressed their wish for more comprehensive information and highlighted the importance of psychological co-care as well as the future perspective. CONCLUSIONS: A relevant proportion of patients with sarcoidosis are inadequately informed about their own disease, particularly with regard to factors impeding quality of life such as fatigue. Efforts are needed to improve the level and quality of information.

The attitudes and practices of physicians caring for patients with rheumatoid arthritis-associated interstitial lung disease: an international survey.

OBJECTIVES: This study sought to determine the level of understanding and opinion among rheumatologist and pulmonologists regarding risk factors, diagnostic approach and treatment of RA-associated interstitial lung disease (RA-ILD). METHODS: We conducted an international electronic survey of rheumatologists and pulmonologists utilizing two separate Redcap-based surveys with questions on the epidemiology, workup and management of RA-ILD as well as ILD screening questions using case-based scenarios directed at rheumatologists. The survey also collected demographic data on participants including their practice setting, years in practice and country of practice. RESULTS: We received a total of 616 responses (354 rheumatologists and 262 pulmonologists) from six continents. There were significant differences in responses between pulmonologists and rheumatologists in estimated prevalence and mortality, risk factors for the development of ILD in RA and medications that are effective or should be avoided. Rheumatologists were much less likely to consider assessment for ILD in high risk, asymptomatic patients compared with high-risk patients with either symptoms or exam findings suggestive of ILD. CONCLUSION: Our study brought to light the variability in disease assessment and clinical practice among providers caring for patients with RA-ILD and indicate that greater education is needed to optimize clinical decision making in the risk assessment, screening and treatment of RA-ILD. Research questions that address appropriate screening and treatment strategies for RA-ILD will be valuable for rheumatologists given their central role in the overall health and lung health of patients with RA.

Endoscopic Valve Therapy in COPD Patients with Hypercapnia.

BACKGROUND: Endoscopic valve therapy has been established as a therapeutic option for patients with severe emphysema. Several randomized controlled trials confirmed the efficacy of this therapeutic approach in COPD patients without significant collateral ventilation. However, patients with clinical relevant hypercapnia were excluded from these trials. AIMS AND OBJECTIVES: Patients with hypercapnia who underwent endoscopic valve treatment were enrolled in this retrospective analysis. The efficacy of valve treatment and its impact on blood gases were analysed. METHODS: COPD patients with mild to severe hypercapnia (pCO2 ≥45 mm Hg) who were treated by endoscopic valve placement at the Thoraxklinik, University of Heidelberg, were enrolled in this retrospective trial. Lung function test (vital capacity [VC], forced expiratory volume in 1 s [FEV1], residual volume [RV]), blood gases (pO2, pCO2), and 6-minute-walk test (6-MWT) were assessed prior to intervention and at 3 and 6 months following valve implantation. RESULTS: 129 patients (mean age 64 ± 7 years) with severe COPD (mean FEV1 26 ± 12% of predicted, mean RV 285 ± 22% of predicted) with hypercapnia (pCO2 ≥45 mm Hg, mean pCO2 50 ± 5 mm Hg) underwent endoscopic valve treatment. 3 and 6 months following intervention, statistical significant improvement was observed in VC, FEV1, RV, and 6-MWT (all p < 0.001). Blood gas analysis revealed a significant improvement of mean pCO2 at 3- and 6-month follow-up (both p < 0.001). 40% of the patients had normal pCO2 values 3 and 6 months following intervention. CONCLUSION: COPD patients with hypercapnia should not be excluded from valve treatment, as the hyperinflation reduction improves the respiratory mechanics and thus leading to improvement of hypercapnia.

[Exacerbation in Idiopathic Pulmonary Fibrosis]. / Akute Exazerbation der idiopathischen Lungenfibrose.

Acute exacerbations (AE) are a life-threatening complication in patients with idiopathic pulmonary fibrosis (IPF). In-hospital mortality is high and the overall prognosis poor. The underlying causes of AE-IPF still remain unclear and there are no focused guidelines for its management. In most cases high-dose steroids combined with an antibiotic therapy are applied. Preventive and palliative measures are very important. Intensive research is necessary to improve management of AE-IPF.

Acute exacerbation of idiopathic pulmonary fibrosis: international survey and call for harmonisation.

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an often deadly complication of IPF. No focussed international guidelines for the management of AE-IPF exist. The aim of this international survey was to assess the global variability in prevention, diagnostic and treatment strategies for AE-IPF.Pulmonologists with ILD expertise were invited to participate in a survey designed by an international expert panel.509 pulmonologists from 66 countries responded. Significant geographical variability in approaches to manage AE-IPF was found. Common preventive measures included antifibrotic drugs and vaccination. Diagnostic differences were most pronounced regarding use of Krebs von den Lungen-6 and viral testing, while high-resolution computed tomography, brain natriuretic peptide and D-dimer are generally applied. High-dose steroids are widely administered (94%); the use of other immunosuppressant and treatment strategies is highly variable. Very few (4%) responders never use immunosuppression. Antifibrotic treatments are initiated during AE-IPF by 67%. Invasive ventilation or extracorporeal membrane oxygenation are mainly used as a bridge to transplantation. Most physicians educate patients comprehensively on the severity of AE-IPF (82%) and consider palliative care (64%).Approaches to the prevention, diagnosis and treatment of AE-IPF vary worldwide. Global trials and guidelines to improve the prognosis of AE-IPF are needed.

A Comparison of Existing Questionnaires for Identifying the Causes of Interstitial and Rare Lung Diseases.

BACKGROUND: A thorough diagnostic process is essential with regard to prognosis and treatment of the more than 200 different types of interstitial lung diseases (ILD). Key to this complex process is a comprehensive medical history. For this, a template is recommended and questionnaires are increasingly used. Yet, the optimal questionnaire has not been established. OBJECTIVES: We aimed to compare well-established questionnaires that are used in the diagnostic process of interstitial and rare lung diseases. METHODS: Via a structured internet search and ILD expert interviews, we identified 6 different questionnaires for the diagnosis of ILDs: the questionnaires developed by the German Respiratory Society (DGP), American College of Chest Physicians (ACCP), National Jewish Health (NJH), Österreichische Röntgengesellschaft/Gesellschaft für Medizinische Radiologie und Nuklearmedizin (OERG), University of California, Los Angeles Health (UCLA), and University of California, San Francisco Medical Center (UCSF). We compared the forms, lengths, and contents of the 6 questionnaires regarding symptoms, comorbidities, drug history, previous ILD therapies, family history, smoking habits, occupational history, exposures, travel history, and former diagnostic procedures. RESULTS: The questionnaires differed in length and content. The UCLA questionnaire focuses on connective tissue diseases extensively, while the NJH questionnaire captures previous diagnostics in detail. The OERG questionnaire is condensed, while the other 5 questionnaires are very detailed. The UCSF questionnaire contains a personal assessment part for the patient. For the majority of the questions, the patient can choose options from a preselected list of possible answers. The DGP questionnaire offers the patient the opportunity to add additional information in the form of free text to some of the key questions. CONCLUSIONS: Questionnaires are an important tool in the diagnostic process of ILDs. Further validation and adjustment to clinical guidelines will help to improve existing questionnaires. Future work must aim to develop an internationally accepted template.

Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases.

BACKGROUND: Fibrosing, non-idiopathic pulmonary fibrosis (non-IPF) interstitial lung diseases (fILDs) are a heterogeneous group of diseases characterized by a different amount of inflammation and fibrosis. Therapy is currently based on corticosteroids and/or immunomodulators. However, response to these therapies is highly variable, sometimes without meaningful improvement, especially in more fibrosing forms. Pirfenidone and nintedanib have recently demonstrated to reduce functional decline in patients with IPF. However, their antifibrotic mechanism makes these two drugs an interesting approach for treatment of fibrosing ILDs other than IPF. OBJECTIVES: We here report our experience with antifibrotic drugs in fibrosing non-IPF ILDs patients having a progressive phenotype during immunosuppressive therapy. METHODS: Patients with a multidisciplinary team diagnosis of fibrosing non-IPF ILDs experiencing a progressive phenotype during treatment with corticosteroids and/or immunomodulators between October-2014 and January-2018 at our tertiary referral Center for ILDs were retrospectively analyzed. Antifibrotic therapy was administered after application with the respective health insurance company and after consent by the patient. Pulmonary-function-tests and follow-up visits were performed every 6 ± 1 months. RESULTS: Eleven patients were treated with antifibrotic drugs (8 males, mean age 62 ± 12.8 years, mean FVC% 62.8 ± 22.3, mean DLCO% 35.5 ± 10.7, median follow-up under antifibrotic treatment 11.1 months). Patients had a diagnosis of unclassifiable ILD in 6 cases, pleuroparenchymal fibroelastosis in 2 cases, idiopathic-NSIP in 1 case, asbestos-related ILD in 1 case and Hermansky-Pudlak syndrome in 1 case. Treatment before antifibrotics consisted of corticosteroids in all patients: 5 combined with Azathioprin, 1 with either methotrexate or cyclophosphamide (i.v.). Ten patients were treated with pirfenidone (2403 mg/die) and 1 with nintedanib (300 mg/die). Median FVC was 56, 56, 50%, at time points - 24, - 12, - 6 before initiation, 44% at time of initiation and 46.5% at 6 months after initiation of antifibrotic treatment. Antifibrotic treatment was generally well tolerated with a need of dose reduction in 2 cases (rash and nausea) and early termination in 3 cases. CONCLUSIONS: Antifibrotic treatment may be a valuable treatment option in patients with progressive fibrosing non-IPF ILD if currently no other treatment options exist. However, prospective, randomized clinical trials are urgently needed to assess the real impact of antifibrotic therapy in these patients.

Associations between comorbidities, their treatment and survival in patients with interstitial lung diseases - a claims data analysis.

BACKGROUND: Interstitial lung diseases (ILDs) are associated with a high burden of disease. However, data on the prognostic impact of comorbidities and comorbidity-related pharmaceutical treatments in patients with various ILDs remain sparse. METHODS: Using longitudinal claims data from a German Statutory Health Insurance Fund, we assessed comorbidity in ILD subtypes and associated drug treatments. Baseline comorbidity was assessed via the Elixhauser Comorbidity Index that was amended by ILD-relevant conditions. Drug treatment was assessed on the substance level using the ATC-codes of drugs prescribed at the time of ILD diagnosis. Subsequently, the comorbid conditions (main analysis) and pharmaceutical substances (secondary analysis) with a meaningful association to survival were identified for the complete ILD cohort and within the subtype strata. For this, we applied multivariate Cox models using a LASSO selection process and visualized the findings within comorbidomes. RESULTS: In the 36,821 patients with ILDs, chronic obstructive pulmonary disease (COPD), arterial hypertension, and ischaemic heart disease (IHD) were the most prevalent comorbidities. The majority of patients with cardiovascular diseases received pharmaceutical treatment, while, in other relevant comorbidities, treatment quotas were low (COPD 46%, gastro-oesophageal reflux disease 65%). Comorbidities had a clinically meaningful detrimental effect on survival that tended to be more pronounced in the case of untreated conditions (e.g. hazard ratios for treated IHD 0.97 vs. 1.33 for untreated IHD). Moreover, comorbidity impact varied substantially between distinct subtypes. CONCLUSIONS: Our analyses suggest that comorbid conditions and their treatment profile significantly affect mortality in various ILDs. Therefore, comprehensive comorbidity assessment and management remains important in any ILD.

Endoscopic Valve Removal >180 Days since Implantation in Patients with Severe Emphysema.

BACKGROUND: Valve implantation provides a reversible effective therapy in a selected group of emphysema patients. Knowing predictors for successful therapy, the rate of treatment failure has decreased. Some patients, however, do not benefit, so that the valves may have to be removed. OBJECTIVES: To assess implant-related events, complications during valve removal, and clinical outcome after endoscopic procedure. METHODS: The data of 76 consecutive emphysema patients who underwent valve removal > 6 months since implantation were collected. RESULTS: Seventy-six patients (mean age 62 years, 54% male) underwent removal of all valves after a mean time of 624 days (193-3,043 days) since implantation. Granulation tissue was observed in 39.5% (30/76) and significant secretion in 34.2% (26/76). In 5.3% (4/76), valve removal was complicated requiring another bronchoscopy in 2 of them. In 5.3% (4/76) of the patients, one valve could not be removed and remained in situ. Bleeding requiring intervention occurred in 3.9% (3/76) during valve removal. Following bronchoscopy, there was a need for antibiotics in 34.2% (26/76), glucocorticosteroids in 1.3% (1/76), and both in 6.6% (5/76) due to productive cough or chronic obstructive pulmonary disease (COPD) exacerbation. Due to respiratory failure, invasive ventilation or noninvasive ventilation was necessary in 2.6% (2/76) and 6.6% (5/76), respectively, following procedure. No statistical significant change in lung function was observed following valve removal. CONCLUSIONS: Valve removal after > 6 months since implantation is feasible and associated with an acceptable safety profile. However, close monitoring of these patients with limited pulmonary reserve is recommended with particular attention to COPD exacerbations and respiratory failure.

[Interstitial lung diseases : Classification, differential diagnosis and treatment approaches in a heterogeneous group of chronic lung disorders]. / Interstitielle Lungenerkrankungen : Klassifikation, Differenzialdiagnostik und therapeutische Ansätze bei einer heterogenen Gruppe chronischer Lungenerkrankungen.

Interstitial lung diseases (ILD) comprise a heterogeneous group of chronic lung disorders of different etiologies that can not only affect the interstitium but also the alveolar space and the bronchial system. According to the "Global Burden of Disease Study" there has been an increase in incidence over the last decades and it is expected that the number of ILD-associated deaths will double over the next 20 years. ILD are grouped into those of unknown cause, e.g. idiopathic pulmonary fibrosis (IPF), and ILD of known cause, which include drug-induced and connective tissue disease-associated ILD as well as granulomatous ILD such as sarcoidosis and hypersensitivity pneumonitis. In addition, some ILD present a progressive fibrosing phenotype, which influences therapeutic decisions. Predominantly inflammatory entities are treated with immunosuppressives, whereas predominantly fibrosing ILD are treated with antifibrotic drugs; in some cases, a combination of both is necessary. The spectrum of differential diagnoses in ILD is broad, but definite diagnosis is essential for treatment selection; therefore, the multidisciplinary ILD board plays a pivotal role.

Establishment of a Tissue-Mimicking Surrogate for Pulmonary Lesions to Improve the Development of RFA Instruments and Algorithms.

(1) Development of radiofrequency ablation (RFA) systems for pulmonary lesions is restricted by availability of human tumor specimens and limited comparability of animal tissue. We aimed to develop a new surrogate tissue overcoming these drawbacks. (2) Reference values for electrical impedance in lung tumor tissue were collected during routine lung tumor RFA (n = 10). Subsequently, a tissue-mimicking surrogate with comparable electrical impedance and facilitating detection of the ablation margins was developed. (3) The mean electrical impedance for all patients was 103.5 ± 14.7 Ω. In the optimized surrogate tissue model consisting of 68% agar solution, 23% egg yolk, 9% thermochromic ink, and variable amounts of sodium chloride, the mean electrical impedance was adjustable from 74.3 ± 0.4 Ω to 183.2 ± 5.6 Ω and was a function (y = 368.4x + 175.2; R2 = 0.96; p < 0.001) of sodium chloride concentration (between 0 and 0.3%). The surrogate tissue achieved sufficient dimensional stability, and sample cuts revealed clear margins of color change for temperatures higher 60 °C. (4) The tissue-mimicking surrogate can be adapted to lung tumor with respect to its electrical properties. As the surrogate tissue allows for simple and cost-effective manufacturing, it is suitable for extensive laboratory testing of RFA systems for pulmonary ablation.

Inhaled Steroids, Sex and Emphysema Index - Clinical Parameters with Impact on the Effectiveness of Valve Implantation in Patients with Severe Emphysema.

Aims and Objectives: Many patients with chronic obstructive lung disease suffer from emphysema. Valve implantation may be a reasonable method in patients presenting advanced emphysema and absent interlobar collateral ventilation (CV). However, other clinical parameters influencing the effectiveness of endoscopic lung volume reduction (ELVR) are not well known. Methods: COPD patients with advanced emphysema who received valve implantation in 2016 were retrospectively analyzed. The following characteristics were collected prior to valve implantation: age, sex, body mass index, presence of allergies, use of inhaled corticosteroids (ICS), lung function parameters, diffusion capacity, 6-minute walk distance (6-MWD), blood gases, COHb, smoking history, and emphysema index (quantitative multi-detector computed tomography). Three months following valve implantation, lung function parameters, diffusion capacity, 6-MWD and blood gases were measured. In this analysis, we evaluated the impact of these variables on an increase in FEV1 and 6-MWT as well as a decrease in RV three months after valve implantation. Results: Overall, 77 COPD patients (57% male, mean age 66, mean FEV1 32%, mean RV 259%) who underwent valve therapy were enrolled. At 3-month follow-up, patients experienced a mean FEV1 increase of 0.09 ± 0.21 L, a mean RV decrease of 0.42 ± 1.80 L and a mean improvement of 8.3 ± 57 m in the 6-MWT. Overall, ICS, sex and emphysema index had an impact on the outcome following ELVR: ICS medication was associated with inferior FEV1 outcome. The higher the emphysema index, the less the RV reduction. Sex was a predictor for change of FEV1 (%), RV (L), and 6-MWT: male patients seem to benefit less than female patients from valve implantation. Conclusion: These findings suggest that ICS, emphysema index and sex are clinical parameters that may be associated with inferior outcome following ELVR. Further studies have to confirm these results to improve patient selection and clinical outcome of ELVR.

Clinical characterization of a novel alpha1-antitrypsin null variant: PiQ0Heidelberg.

The clinical characterization of a null variant of SERPINA1 - PiQ0Heidelberg - resulting in alpha1-antitrypsin (AAT) deficiency is described. This rare mutation (c.-5+5 G > A) has been previously identified but not clinically described. The 77 year-old female patient had GOLD-3, Group B COPD, severe destructive panlobular emphysema and newly observed respiratory failure on exertion at the time the genetic analysis was performed. Serum AAT level was 0.1 g/L (reference 0.9-2.0 g/L). Isoelectric focusing showed only the Z-protein indicating that this was a null mutation. The patient has started AAT replacement. Early screening and identification of AAT deficiency would allow for earlier intervention.

Outcomes and Incidence of PF-ILD According to Different Definitions in a Real-World Setting.

Background: Almost one-third of fibrosing ILD (fILDs) have a clinical disease behavior similar to IPF, demonstrating a progressive phenotype (PF-ILD). However, there are no globally accepted criteria on the definition of a progressive phenotype in non-IPF fILD yet. Four different definitions have been used; however, no internationally accepted definition currently exists. Research Question: To compare the clinical and functional characteristics of progressive fILD according to the currently available definitions. Study design and methods: Cases of fILD were identified retrospectively from the database of the tertiary referral center for ILD in Heidelberg. Lung function, clinical signs of progression, and radiological changes were evaluated. Patients with fILD were considered to have progression according to each of the four available definitions: Cottin (CO), RELIEF (RE), INBUILD (IN), and UILD study. Lung function changes, expressed as mean absolute decline of FVC%, were reported every 3 months following diagnosis and analyzed in the context of each definition. Survival was also analyzed. Results: A total of 566 patients with non-IPF fILD were included in the analysis. Applying CO-, RE-, IN-, and UILD-definitions, 232 (41%), 183 (32%), 274 (48%), and 174 (31%) patients were defined as PF-ILD, respectively. RE- and UILD-criteria were the most stringent, with only 32 and 31% patients defined as progressive, while IN- was the most broad, with almost 50% of patients defined as progressive. CO- definition was in-between, classifying 41% as progressive. PF ILD patients with a UILD definition had worse prognosis. Interpretation: Depending on the definition used, the existing criteria identify different groups of patients with progressive fILD, and this may have important prognostic and therapeutic implications.

Management of Acute Exacerbation of Idiopathic Pulmonary Fibrosis in Specialised and Non-specialised ILD Centres Around the World.

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide. Material and Methods: Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians' institutions. Results: Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods. Conclusion: Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.

Interventional therapy in patients with severe emphysema: evaluation of contraindications and their incidence.

BACKGROUND: Endoscopic and surgical interventions may be beneficial for selected patients with emphysema. Rates of treatment failure decrease when the predictors for successful therapy are known. The aim of the study was to evaluate the number of patients with severe emphysema who were not eligible for any intervention, and the reasons for their exclusion. METHODS: The study was a retrospective analysis of 231 consecutive patients with advanced emphysema who were considered for interventional therapy in 2016 at the Thoraxklinik, Heidelberg, Germany. The reasons for not receiving valve or coil therapy were assessed for all patients who did not receive any therapy. RESULTS: Of the 231 patients, 50% received an interventional therapy for lung volume reduction (LVR) (82% valve therapy, 6% coil therapy, 4.3% polymeric LVR or bronchial thermal vapour ablation, 4.3% total lung denervation, and 3.4% lung volume reduction surgery [LVRS]). A total of 115 patients did not undergo LVR. Out of these, valve or coil therapy was not performed due to one or more of the following reasons: incomplete fissure in 37% and 0%; missing target lobe in 31% and 30%; personal decision in 18% and 28%; pulmonary function test results in 8% and 15%; ventilatory failure in 4% and 4%; missing optimal standard medical care and/or continued nicotine abuse in 4% and 3%; general condition too good in less than 1% and 3%; cardiovascular comorbidities in 0% and 3%; age of patient in 0% and less than 1%. Both techniques were not performed due to one or more of the following reasons: solitary pulmonary nodule(s)/consolidation in 27%; bronchopathy in 7%; neoplasia in 2%; destroyed lung in 2%; prior LVRS in less than 1%. CONCLUSIONS: The main reason for not placing valves was an incomplete fissure and for coils a missing target lobe. Numerous additional contraindications that may exclude a patient from interventional emphysema therapy should be respected.